Emerging evidence points to accelerated biological aging as a potential mechanism in the pathogenesis of cardiovascular disease (CVD). Traditionally, biological aging has been viewed as immutable and synonymous with chronological aging. However, recent studies suggest that markers of biological aging can be altered and accelerated in the presence of certain CVD risk factors, suggesting a link between biological aging and vascular deterioration. Age is a known dominant risk factor for cardiovascular disease; however, there are shortcomings in our present-day understanding of why age is a powerful determinant for chronic disease. Identifying the elements that comprise the complex aging process is crucial for CVD prevention, particularly modifiable elements such as diet. The Mediterranean diet has been shown to reduce inflammation and oxidative stress, suggesting its potential to decelerate the biological aging process that underlies atherosclerosis. However, no previous study has systematically examined markers of accelerated aging with the intent to explore the cardioprotective mechanisms of the Mediterranean diet. In the proposed study, we hypothesize that the beneficial effects of the Mediterranean diet can be attributed to 1) improved telomere preservation and 2) reduced accumulation of advanced glycation end products (AGEs). We will investigate these aging mechanisms by comparing twin pairs discordant for adherence to the Mediterranean diet (MD). Further analysis would explore the degree to which genetic and shared environmental factors influence the impact of diet on accelerated aging. Among a sample of 640 middle-aged male twins asymptomatic of CVD, we aim: 1) To compare biomarkers of biological aging between twins with higher MD scores and co-twins with lower scores; 2) To determine whether biomarkers of biological aging explain observed differences in subclinical measures of CVD between twins with higher MD scores and co-twins with lower scores; and 3) To investigate the extent to which genetic and shared environmental factors contribute to the link between adherence to the Mediterranean diet and accelerated aging. As a secondary aim, we will investigate the above processes using two alternative dietary metrics, including the Dietary Approaches to Stopping Hypertension (DASH) score and Healthy Eating Index, in order to examine the consistency of our results with other composite measures of a healthy diet. This study opens a novel and important line of investigation, examining how adherence to a healthy diet could decrease the speed of biological aging and prevent cardiovascular disease. PUBLIC HEALTH RELEVANCE: The proposed study represents a novel and compelling opportunity to systematically examine accelerated biological aging as a potential mechanism linking the Mediterranean diet to its cardioprotective effects. Unearthing this underlying pathway will be important for substantiating the public health relevance of a healthy diet, and for designing interventions targeted at CVD prevention and heath promotion, since diet modification could be a safe, economic and relatively sustainable approach to mitigate CVD risk and halt or reverse early vascular aging.